The Knights of the Round Table hypothesis of tumour suppressor gene function--noble sacrifice or sexual dalliance: genes, including p53, BRCA1/2 and RB have evolved by horizontal and vertical transmission of mating factor genes and are involved in gametogenesis, implantation, development and tumourigenesis.
The genes involved in negative cell cycle regulation and familial tumour susceptibility including APC, BRCA, p53, RB, WT1 are unique and have no homologies with other genes. Our hypothesis suggests they originated from mating factor genes, which halted cell division in response to stress to generate genetic diversity by sexual mechanisms. Some have evolved principally by vertical transmission (mismatch repair), others by horizontal transmission via mobile elements, predominantly in oocytes. We demonstrate amplification in human extra-embryonic tissues in fetus and mother in implantation; in the developing fetus, differing tissue-specific patterns are seen, especially between testis and ovary. We suggest that the fetus is susceptible to maternal transmission of infections including CMV, malaria, trypanosomes, whose sequences occur within these genes. In head and neck cancers, we demonstrate specific patterns of loss or instability involving up to seven different TSG. We suggest mechanisms of tumourigenesis involve transposable elements and episome formation, leading to loss of negative cell cycle regulation and exit from G0.
Gosden
C M
CM
Department of Obstetrics and Gynaecology, University of Liverpool, P.O. Box 147, Liverpool L69 3BX, UK.
Liloglou
T
T
Nunn
J
J
Gardener
D
D
Nickson
P
P
Crampton
J M
JM
Field
J K
JK
D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D004251:DNA Transposable Elements / Q000235:genetics; D018562:Disease Transmission, Infectious; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D019398:Genes, BRCA1 / Q000502:physiology; D024522:Genes, BRCA2 / Q000502:physiology; D016161:Genes, Retinoblastoma / Q000502:physiology; D016147:Genes, Tumor Suppressor / Q000502:physiology*; D016158:Genes, p53 / Q000502:physiology; D018095:Germ-Line Mutation; D006801:Humans; D018445:Infectious Disease Transmission, Vertical; D008297:Male; D000072235:Mating Factor; D018895:Microsatellite Repeats; D010455:Peptides / Q000235:genetics*; D010684:Philosophy
D004251:DNA Transposable Elements; D010455:Peptides; D000072235:Mating Factor